PART I: The synthesis of reactive epoxides of the arene oxide and oxepin class will be carried out. Nucleophilic additions to these reactive classes of epoxides will be studied in relation to the carcinogenic activation of polycyclic aromatic hydrocarbons, and in relation to the total synthesis of antiviral agents potentially useful in the treatment of viral caused cancer. PART II: Model systems will be studied to mimic the mechanism of carcinogenic activation of polycyclic aromatic hydrocarbons and the mechanism of similar oxidative transformations by the flavin cofactored monooxygenases. PART III: Reactive crown ethers, macrocyclic reagents capable of both complexing and reacting selectively with substrates in nonpolar media, will be used in mechanistic and synthetic studies. These will include further studies of the mechanism of action of flavins in enzyme oxidation systems and the development of an efficient and general macrolide synthesis.